Liquid Biopsy Detects Early Molecular Response and Predicts Benefit to First-Line Chemotherapy plus Cetuximab in Metastatic Colorectal Cancer: PLATFORM-B Study
Por:
Vidal J., Fernández-Rodríguez M.C., Casadevall D., García-Alfonso P., Páez D., Guix M., Alonso V., Cano M.T., Santos C., Durán G., Elez E., Manzano J.L., Garcia-Carbonero R., Ferreiro R., Losa F., Pineda E., Sastre J., Rivera F., Bellosillo B., Tabernero J., Aranda E., Salazar R., Montagut C.
Publicada:
1 ene 2023
Resumen:
PURPOSE: Chemotherapy plus anti-EGFR is standard first-line therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC), but biomarkers of early response are clinically needed. We aimed to define the utility of ctDNA to assess early response in patients with mCRC receiving first-line anti-EGFR therapy. EXPERIMENTAL DESIGN: Prospective multicentric study of tissue patients with RAS wt mCRC treated with first-line chemotherapy plus cetuximab undergoing sequential liquid biopsies. Baseline and early (C3) ctDNA were analyzed by NGS. Trunk mutations were assessed as surrogate marker of total tumor burden. RAS/BRAF/MEK/EGFR-ECD were considered mutations of resistance. ctDNA results were correlated with clinical outcome. RESULTS: One hundred patients were included. ctDNA was detected in 72% of patients at baseline and 34% at C3. Decrease in ctDNA trunk mutations correlated with progression-free survival (PFS; HR, 0.23; P = 0.001). RAS/BRAF were the only resistant mutations detected at C3. An increase in the relative fraction of RAS/BRAF at C3 was followed by an expansion of the RAS clone until PD, and was associated with shorter PFS (HR, 10.5; P < 0.001). The best predictor of response was the combined analysis of trunk and resistant mutations at C3. Accordingly, patients with "early molecular response" (decrease in trunk and decrease in resistant mutations) had better response (77.5% vs. 25%, P = 0.008) and longer PFS (HR, 0.18; P < 0.001) compared with patients with "early molecular progression" (increase in trunk and/or increase in resistant mutations). CONCLUSIONS: ctDNA detects early molecular response and predicts benefit to chemotherapy plus cetuximab. A comprehensive NGS-based approach is recommended to integrate information on total disease burden and resistant mutations. See related commentary by Eluri et al., p. 302. ©2022 American Association for Cancer Research.
Filiaciones:
Vidal J.:
Medical Oncology Department, Hospital del Mar, Institut Mar Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, Barcelona, Spain
Fernández-Rodríguez M.C.:
Pathology Department, Hospital del Mar-IMIM, Barcelona, Spain
Casadevall D.:
Medical Oncology Department, Hospital del Mar, Institut Mar Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, Barcelona, Spain
García-Alfonso P.:
Medical Oncology Department, Hospital Gregorio MarañónMadrid, Spain
Páez D.:
Medical Oncology Department, H. Santa Creu i Sant Pau, Barcelona, Spain
Guix M.:
Medical Oncology Department, Hospital del Mar, Institut Mar Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, Barcelona, Spain
Alonso V.:
Medical Oncology Department, H. Miguel Servet, Zaragoza, Spain
Cano M.T.:
Medical Oncology Department, IMIBIC, Reina Sofía Hospital, University of CordobaCordoba, Spain
Santos C.:
Medical Oncology Department, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL)-CIBERONC, Barcelona, Spain
Durán G.:
Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain
Elez E.:
Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
Manzano J.L.:
Medical Oncology Department, ICO, H. Germans Trias i Pujol, Barcelona, Spain
Garcia-Carbonero R.:
Medical Oncology Department, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), UCM, Hospital Universitario 12 de OctubreMadrid, Spain
Ferreiro R.:
Medical Oncology Department, Hospital Ramón y CajalMadrid, Spain
Losa F.:
Medical Oncology Department, Hospital Sant Joan Despí - Moisès Broggi, Spain
Pineda E.:
Medical Oncology Department Hospital Clínic, Barcelona, Spain
Sastre J.:
Medical Oncology Department, Hospital Universitario Clínico San CarlosMadrid, Spain
Rivera F.:
Medical Oncology Department Hospital Marqués de Valdecilla, IDIVALSantander, Spain
Bellosillo B.:
Pathology Department, Hospital del Mar-IMIM, Barcelona, Spain
Tabernero J.:
Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
Aranda E.:
Medical Oncology Department, IMIBIC, Reina Sofía Hospital, University of CordobaCordoba, Spain
Salazar R.:
Medical Oncology Department, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL)-CIBERONC, Barcelona, Spain
Montagut C.:
Medical Oncology Department, Hospital del Mar, Institut Mar Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, Barcelona, Spain
Green Submitted, All Open Access; Green
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